Studies towards the first total synthesis of the polyene antibiotic bacillaene and simplified analogues Maximilian Guhlke, Dirk Menche University of Bonn, Germany Bacillaene is a potent polyene antibiotic produced by members of the Bacillus family, first isolated in 1995. 1 Its biosynthetic pathway was fully elucidated in 2010, revealing a massive investment of cellular resources required for its production, suggesting a crucial biological function. 2,3 Despite its high potential, the natural product itself is exceedingly labile, rendering the total synthesis of bacillaene a formidable challenge. A stereochemical proposal of two of the three stereogenic centers will be presented, that was based on bioinformatics gene cluster analyses. Furthermore, we have developed an innovative iterative cross-coupling approach utilizing a method that enables a rapid assembly of the core structure. Three consecutive cross-couplings are performed without additional manipulation of intermediates, providing a streamlined route towards complex and labile targets. Furthermore, a stereoselective Peterson olefination method, originally developed by Fürstner, will be presented as a potential strategy for the introduction of the sensitive (Z)-enamide functionality into the target molecule. Preliminary results support the effectiveness of this methodology, laying the groundwork for optimization of conditions and exploration of analogs with improved stability and activity. The strategies, tactics and procedures discussed on the poster will be of high relevance to develop a first total synthesis of this important polyene antibiotic as well as carefully selected and more stable analogues to further evaluate the potent biological properties of this polyketide. Also, these tactics may find further applications for synthesis of related polyenes as well as sensitiveenamides.
References 1. S. Patel, S. Huang, S. Fisher, D.S. Pirnik, C. Aklonis, L. Dean, E. Meyers, P. Fernandes, F. Mayerl, Antibiotics 1995 , 48 , 997–1003. 2. R. A. Butcher, F. C. Schroeder, M. A. Fischbach, P. D. Straight, R. Kolter, C. T. Walsh, J. Clardy, Proc. Natl. Acad. Sci. 2007 , 104 , 1506–1509. 3. J. Moldenhauer, D. Gotz, C. R. Albert, S. K. Bischof, K. Schneider, R. D. Süssmuth, M. Engeser, H. Gross, G. Bringmann, J. Piel, Angew. Chem. 2010 , 122 , 1507–1509.
P39F
© The Author(s), 2023
Made with FlippingBook Learn more on our blog